Keytruda....Working for MSS....Mutation Burden is the Key

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boswind
Posts: 71
Joined: Fri Apr 11, 2014 12:04 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby boswind » Tue Mar 12, 2019 3:15 pm

Cynthia,

Thank you for creating this thread, which led me an opportunity to take Keytruda off label.

I visited my Onc.'a office last week. He told me because it would take a week or so to complete the paper work with my insurance company I would have an infusion of Keytruda this Thur.

Also, my onc. told my TMB was 12 instead of 10.24. The hospital did the gene analysis in house instead of sending the tissue sample to Foundation One. I guess the lab made a correction? The tissue sample from my liver biopsy done 4 years ago was used for the analysis.

Further, based on the info from Foundation One and online literature, I believe that my current TMB could actually be around 15 because I have gone through 2 lines of targeted chemos since my liver biopsy.
01.24.14 Male, DX @54 Rectosigmoid Cancer, MRI: T3N0M0
03.19.14 Completed 5-week Radia+Xeloda
05.07.14 Had surgery
02.25.15 CT showed stage 4.
03.15 - 08.15, folfox + Avastin
08.15 - 07.17, 5FU+leucovorin+Avastin
07.17 - 01.18, Folfuri + Avastin
02.18 - 03.19, Centuximab + Irinotecan
90 rounds of chemos received (as of 12.27.18)
MSS, KRAS wt, BRAF wt
03.19 - 05.19, Keytruda
05.19 - 9.19, Folfox+Avastin
10.22.19 - rechallenge Centuximab+Irinotecan

stu
Posts: 1207
Joined: Sat Aug 17, 2013 5:46 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby stu » Tue Mar 12, 2019 4:21 pm

Hi Cynthia ,
I have been following your story and able to share it with my friend who is having treatment for stage 4 lung cancer . She is responding really well to Keytruda .

I thought you might be interested to know there is a clinical trial now open here for Immuotherapy with MSS patients !! How good is that !
Take care,
Stu
supporter to my mum who lives a great life despite a difficult diagnosis
stage4 2009 significant spread to liver
2010 colon /liver resection
chemo following recurrence
73% of liver removed
enjoying life treatment free
2016 lung resection
Oct 2017 nice clear scan . Two lung nodules disappeared
Oct 2018. Another clear scan .

Pyro70
Posts: 155
Joined: Mon Jan 21, 2019 4:25 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Pyro70 » Tue Mar 12, 2019 4:47 pm

Boswind and all,

Have you figured out if there is any correlation between the number of somatic variants/mutations listed and TMB? I noticed that Cynthia listed the 12 variants and her TMB is 12. I know gremline variants (those from your parents) don’t count toward TMB since the immune system likely doesn’t react to them being abnormal. I’m also aware that there isn’t a single standard of how to measure TMB and each company does it differently.

I had a NGS performed by Tempus. It says my TMB is only 3.4. However, I have 21 somatic variants so I’m wondering if Tempus’s TMB is an apples-to-apples comparison to Foundation One.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Danielito82
Posts: 28
Joined: Sat Aug 11, 2018 1:53 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Danielito82 » Tue Mar 12, 2019 5:32 pm

Really? ??....a new clinical trial for mss? ?
In which country? ?..this is a great news ...new hope :D ...I would be really grateful if you could give me more info....
Thank you for sharing! !

Always ...walk on!!

stu
Posts: 1207
Joined: Sat Aug 17, 2013 5:46 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby stu » Tue Mar 12, 2019 5:41 pm

The UK which really is a surprise as we are way behind with accessing it for MSI patients yet here is this clinical trial!! I know someone going on it too who has failed first and second line chemo . Quite exciting !!
Stu
supporter to my mum who lives a great life despite a difficult diagnosis
stage4 2009 significant spread to liver
2010 colon /liver resection
chemo following recurrence
73% of liver removed
enjoying life treatment free
2016 lung resection
Oct 2017 nice clear scan . Two lung nodules disappeared
Oct 2018. Another clear scan .

Danielito82
Posts: 28
Joined: Sat Aug 11, 2018 1:53 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Danielito82 » Tue Mar 12, 2019 6:39 pm

Wow..that's great! !!!!!...I'm Italian but I live in Manchester uk and I'm treated at the Christie hospital but I'm also in touch with Italian doctors. .but no one told me anything about it although I did ask....

Thanks again! !!!

stu
Posts: 1207
Joined: Sat Aug 17, 2013 5:46 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby stu » Wed Mar 13, 2019 2:26 am

Let me check but I think Christie’s is one of the trial locations !!!
supporter to my mum who lives a great life despite a difficult diagnosis
stage4 2009 significant spread to liver
2010 colon /liver resection
chemo following recurrence
73% of liver removed
enjoying life treatment free
2016 lung resection
Oct 2017 nice clear scan . Two lung nodules disappeared
Oct 2018. Another clear scan .

Danielito82
Posts: 28
Joined: Sat Aug 11, 2018 1:53 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Danielito82 » Wed Mar 13, 2019 3:17 am

I love this group!!!. .you guys are so amazing. ..always ready to help....
Thanks so much! !!!

WarriorSpouse
Posts: 204
Joined: Tue Aug 16, 2016 9:02 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby WarriorSpouse » Wed Mar 13, 2019 10:50 am

Cynthia,
I just wanted to thank you for sharing your post and experiences here. My wife is MSS and has had confirmed recurrence and we are currently waiting on genetic testing results on her most recent biopsy. This forum is a wonderful resource because of participants like yourself. Thank you for sharing hope and current trends. We learn so much from each other here. Thanks again!
WS
D/H 47 years old, 10/2014, Stage IV M/CRC, nodes 12/15, para-aortic, 5 cm sigmoid resection, positive Virchow. KRAS mut, MSS, Highly Differentiated, Lynch Neg, 5FU/LV and Avastin 1 YR (Oxi for 5 months), Zeloda/Bev since 01/2016. 02/2019 recurrence para-nodes, back to 5FU/LV Oxy/Bev. It is working again. "...Perseverance is not a long race; it is many short races one after the other."-Walter Elliot

boswind
Posts: 71
Joined: Fri Apr 11, 2014 12:04 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby boswind » Wed Mar 13, 2019 1:35 pm

If you search clinicaltrials.gov with terms such as "TMB", “tumor mutation burden”, “tumor mutational burden”, “tumor mutation load”, or “tumor mutational load”, you will see quite a few TMB-H clinical trials that are on-going or to start. Unfortunately, there is only one trial in the US that we may be eligible for (but not yet to recruit):
--
A Randomized, Open-Label, Phase 2 Study of Nivolumab in Combination With Ipilimumab or Nivolumab Monotherapy
in Participants With Advanced or Metastatic Solid Tumors of TMB-H
Phase 2
NCT03668119
Not yet recruiting in the US
--
I found the countries that have the most TMB-H clinical trials include Italy and China.
01.24.14 Male, DX @54 Rectosigmoid Cancer, MRI: T3N0M0
03.19.14 Completed 5-week Radia+Xeloda
05.07.14 Had surgery
02.25.15 CT showed stage 4.
03.15 - 08.15, folfox + Avastin
08.15 - 07.17, 5FU+leucovorin+Avastin
07.17 - 01.18, Folfuri + Avastin
02.18 - 03.19, Centuximab + Irinotecan
90 rounds of chemos received (as of 12.27.18)
MSS, KRAS wt, BRAF wt
03.19 - 05.19, Keytruda
05.19 - 9.19, Folfox+Avastin
10.22.19 - rechallenge Centuximab+Irinotecan

bdoyle
Posts: 3
Joined: Sun Dec 09, 2018 9:50 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby bdoyle » Wed Mar 13, 2019 2:00 pm

You can look into the TAPUR trial for Keytruda. It is sponsored by ASCO and open almost everywhere with new cohorts. Google TAPUR and ASCO. However, be careful with immunotherapies; they can exclude you from a lot of trials if you fail but make you eligible for a few others. However, the scale is heavier towards exclusion. I have 13 TMB and appear to have failed keytruda as a
monotherapy. I have had 3 infusions and my CEA continues to rise and tumors continue to increase 50% month-over-month.

Pyro70
Posts: 155
Joined: Mon Jan 21, 2019 4:25 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Pyro70 » Wed Mar 13, 2019 5:27 pm

bdoyle wrote:You can look into the TAPUR trial for Keytruda. It is sponsored by ASCO and open almost everywhere with new cohorts. Google TAPUR and ASCO. However, be careful with immunotherapies; they can exclude you from a lot of trials if you fail but make you eligible for a few others. However, the scale is heavier towards exclusion. I have 13 TMB and appear to have failed keytruda as a
monotherapy. I have had 3 infusions and my CEA continues to rise and tumors continue to increase 50% month-over-month.


I’m sorry to hear keytruda hasn’t achieved the desired response. I’m not sure if you are aware, but a minority of patients have a delayed response to immunotherapy:

https://www.onclive.com/publications/on ... -responses
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Pyro
Posts: 303
Joined: Mon Oct 12, 2015 7:40 pm
Location: Tucson, AZ

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Pyro » Thu Mar 14, 2019 9:13 am

bdoyle wrote:You can look into the TAPUR trial for Keytruda. It is sponsored by ASCO and open almost everywhere with new cohorts. Google TAPUR and ASCO. However, be careful with immunotherapies; they can exclude you from a lot of trials if you fail but make you eligible for a few others. However, the scale is heavier towards exclusion. I have 13 TMB and appear to have failed keytruda as a
monotherapy. I have had 3 infusions and my CEA continues to rise and tumors continue to increase 50% month-over-month.


That’s around 9 weeks? I’ve read it can take 12, are you going to continue through the 12 weeks are look for something else?
Aug 2015- Stage 4 CC with liver Mets(38/m)
Sep 2015- Avastin/Folfox/Iron
Dec 2015-Not liver surgery candidate
Jan 2016- Erbitux/Folfiri, 2nd opinion at MDA in TX
Feb 2016 -MDA liver surgery
Mar 2016 -30% of left lobe rem, PVE
May 2016 - 70% of liver rem
Jun 2016-Rad
Jan 2017-perm colost @MDA
Jul 2017-Erb/FOLFURI
Nov 2017 -Lung & Liver ablations@MDA
Jan 2018 -Xeloda & Avastin mx
Jul 2018-Avast/FOLFURI
Sep 2018-Rad
Mar 2019 - Keytruda fail
Jun 2019 - FOLFURI
Aug 2019 - No more, quality time!

stu
Posts: 1207
Joined: Sat Aug 17, 2013 5:46 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby stu » Thu Mar 14, 2019 4:08 pm

Hi ,
Manchester is one of five locations . It’s open to May 2019 . It’s quite a small trial . Phase1 I think but Phaze 2 maybe in the pipeline .

Maybe only allowing people who have not had success with chemo to enter . Not sure though .

Take care ,

Stu
supporter to my mum who lives a great life despite a difficult diagnosis
stage4 2009 significant spread to liver
2010 colon /liver resection
chemo following recurrence
73% of liver removed
enjoying life treatment free
2016 lung resection
Oct 2017 nice clear scan . Two lung nodules disappeared
Oct 2018. Another clear scan .

Danielito82
Posts: 28
Joined: Sat Aug 11, 2018 1:53 pm

Re: Keytruda....Working for MSS....Mutation Burden is the Key

Postby Danielito82 » Fri Mar 15, 2019 7:04 am

Thanks stu for the info!!
I'll ask to my onc about it. ...

Grazieeee

Always walk on


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